PKR-dependent and -independent mechanisms are involved in translational shutoff during Sindbis virus infection. Academic Article uri icon

Overview

abstract

  • The replication of Sindbis virus (SIN) profoundly affects the metabolism of infected vertebrate cells. One of the main events during SIN infection is the strong inhibition of translation of cellular mRNAs. In this study, we used a combination of approaches, including the study of SIN replication in PKR(-/-) mouse embryo fibroblasts or in the presence of an excess of catalytically inactive PKR. We show that the PKR-dependent inhibition of translation is not the only and most likely not the major pathway mediating translational shutoff during SIN infection. The PKR-independent mechanism strongly affects the translation of cellular templates, whereas translation of SIN subgenomic RNA is resistant to inhibition, and this leads to a benefit for viral replication. Our findings suggest that both PKR-dependent and non-PKR-dependent mechanisms of SIN-induced translational shutoff can be manipulated by using SIN replicons expressing mutated SIN nsP2 or kinase-defective PKR. Specifically, we show that expression of heterologous genes from SIN-based and most likely other alphavirus-based replicons can be increased by downregulating both the PKR-dependent and PKR-independent translational shutoffs.

publication date

  • August 1, 2004

Research

keywords

  • Fibroblasts
  • Gene Expression Regulation
  • Protein Biosynthesis
  • Sindbis Virus
  • eIF-2 Kinase

Identity

PubMed Central ID

  • PMC479073

Scopus Document Identifier

  • 3543049963

Digital Object Identifier (DOI)

  • 10.1128/JVI.78.16.8455-8467.2004

PubMed ID

  • 15280454

Additional Document Info

volume

  • 78

issue

  • 16